The molecular genetics component of Program 1 will build on the progress of this aspect of the Program over the past five years. For example, super-enhancers particularly those that appear to control many activated oncogenes, offer possible new approaches to the diagnosis and treatment of cancer. Large non-coding RNAs control gene expression is a focus of research in this Program, and these are likely to control important aspects of tumor genesis. CRISPR technology is a very powerful tool for research on cancer, allowing rapid mutation of many genes in parallel and physically targeting transcription-modulating signals to specific sites on the genome. Small non-coding RNAs such as microRNAs are tightly integrated into networks that control the malignant state, but this has neither been fully illuminated nor set into the regulatory networks of genes important in cancer. These topics and others are developed in the research sections of 1) roles of transcriptional super-enhancers in control of cell identity and cancer, 2) large noncoding RNAs and cancer, 3) probing cancer genomes with CRISPR technology, 4) small non-coding RNAs and cancer, 5) cancer genome and transcriptome analysis, and 6) synthetic biology and cancer. The immunology component of Program 1 features a deep integration of engineering approaches with immunological science to advance our understanding of the interaction of cancer cells with the immune system and develop new forms of immunotherapy. The immunoengineering perspective is a particular strength of the Program and is an instantiation of the broader phenomenon of convergence between engineering and the life sciences in the Koch Institute. Immunology, in particular, is a field that is amenable to both analytical engineering and design engineering. Decoding communications between cells in the immune system using principles of chemical engineering and synthesis and engineering synthetic vaccines using cues from natural immunity are strengths of the Program. These topics and others are discussed in sections 1) therapeutic cancer vaccine development, 2) synergistic antibody/IL-2 immunotherapy, 3) mouse/human models of follicular B cell lymphoma, 4) whole exome sequencing of CTCs as a window into metastatic cancer. Program 1 has 16 Members from 5 Academic Departments at the School of Science or School of Engineering at MIT. The Membership has a cancer-related funding base of $ 24,934,945 TDC. From 4/1/2009, the Membership of Program 1 published 508 cancer-related articles. Of those, 107, or 21%, have involved multiple members; 45, or 8.9%, intra-programmatic, and, 62 or 12.2%, inter-programmatic; 4 are both intra- and interprogrammatic.